This proposal describes a five-year training program for the development of an academic career in Medical Genetics. The principal investigator is a board eligible pediatrician with a Ph.D. in Biochemistry with a long-standing interest in signal transduction involved in early differentiation. She has pursued relevant clinical and research training with a long-term goal of contributing to the understanding of the molecular mechanisms involved in human development and disease. This research proposal will expand the candidate's research background to the field of mammalian genetics and development. The studies outlined in this proposal will address the role of quaking, a KH domain RNA binding protein, in vascular and cardiac development. Vascular malformations are estimated to affect between 0.3-0.5 percent of the population while congenital heart defects affect an additional 1 percent of the population. In addition, vascular development is important for would healing, ischemic heart disease, diabetes, retinopathy and tumor growth and is a currently a critical area of medical research. This proposal will be undertaken in the Department of Molecular and Human Genetics at Baylor College of Medicine that has an excellent record in the training of Clinical Postd6ctoral Fellows for independent careers in academic science, in addition to being renowned for mouse genetics and developmental embryology. Dr. Monica Justice, a well-established researcher in the field of mouse developmental genetics will be the primary sponsor of the candidate. Dr. Justice is a pioneer in mouse ENU mutagenesis, who is currently directing the NIH-funded Mouse Mutagenesis and Phenotyping Center for Developmental Defects. To complement the mouse genetics expertise, Dr. Karen Hirschi, a faculty member in the Department of Cell Biology, will cosponsor the applicant. Dr. Hirschi brings to the project in depth knowledge of vascular development and the use of in vitro model systems to delineate the cellular interactions involved early vessel formation. An advisory committee comprised of senior faculty members both within the applicants department and outside of Baylor has been established to help guide her career development. These well established faculty members have supervised over 100 trainees between them and will provide solid mentoring for Dr. Northrop's scientific advancement. Through the combination of supervised research, scientific interchange, selected coursework and seminar series within this environment, the candidate will obtain the training necessary to transition to an independent investigator.